The present invention relates to nanoparticles comprising a poorly water-soluble drug, ethylcellulose, and a bile salt.
It is known that poorly water-soluble drugs may be formulated as nanoparticles. Nanoparticles are of interest for a variety of reasons, such as to improve the bioavailability of poorly water-soluble drugs, to provide targeted drug delivery to specific areas of the body, to reduce side effects, or to reduce variability in vivo.
A variety of approaches have been taken to formulate drugs as nanoparticles. One approach is to decrease the size of crystalline drug by grinding or milling the drug in the presence of a surface modifier. See, e.g., U.S. Pat. No. 5,145,684. Another approach to forming nanoparticles is to precipitate the drug in the presence of a film forming material such as a polymer. See, e.g., U.S. Pat. No. 5,118,528.
Nanoparticles containing a drug and ethylcellulose are known in the art. See, for example, U.S. Pat. Nos. 5,919,408, 5,118,528, EP 1 180 062 B1, and Bodmeier and Chen (J. Controlled Release, 12, (1990) 223-233). The prior art nanoparticle formulations often included a surfactant to stabilize the nanoparticles.
While these formulations may be functional, nevertheless there remain a number of problems associated with the use of nanoparticles to deliver pharmaceutical compounds to the body. The nanoparticles must be stabilized so that they do not aggregate into larger particles. Often surface modifiers such as surfactants are used to stabilize the nanoparticles, but such materials can have adverse physiological effects when administered in vivo. In addition, without a surface modifier present, the surface of the nanoparticles is unprotected, leading to a decrease in performance and stability. Additionally, when formulated as a dry material, the composition should spontaneously form nanoparticles when the composition is added to an aqueous use environment.
Accordingly, there is still a continuing need for nanoparticles that are stable, in the sense of not forming crystalline drug over time or aggregating into larger particles, and that improve the bioavailability of low-solubility drugs.